Iron Supplementation with Ferrous Sulfate or Ferrous Bisglycinate for 12 Weeks Does Not Influence Group B Streptococcus Colonization in Cambodian Women: A Secondary Analysis of a Randomized Controlled Trial

Abstract

Background: Iron deficiency in women of reproductive age can have severe adverse perinatal consequences. Although iron supplementation can be effective at treating iron deficiency, excess unabsorbed iron in the gut may also promote colonization by enteropathogens such as Group B Streptococcus (GBS), increasing the potential risk of maternal and neonatal infection.

Objectives: We examined whether 12 wk of supplementation with 18 mg elemental iron as ferrous bisglycinate, 60 mg as ferrous sulfate, or a placebo differentially influences GBS colonization in Cambodian women of reproductive age.

Methods: This study is a secondary analysis of a randomized controlled trial conducted in 25 villages in 3 districts of Kampong Thom province, Cambodia, including 144 nonpregnant women (18‒45 y) who received 18 mg of elemental iron as ferrous bisglycinate, 60 mg ferrous sulfate, or placebo for 12 wk. GBS colonization was assessed by real-time quantitative polymerase chain reaction targeting the cfb gene (which encodes the Christie-Atkins-Munch-Peterson [CAMP] factor, an indicator of GBS colonization) from stool collected at baseline and 12 wk. Cycle threshold values were compared within and across groups using Kruskal-Wallis and Wilcoxon signed-rank tests.

Results: No changes in cfb expression were detected between baseline and endline within any treatment arm, nor were there differences across groups at 12 wk. However, regional differences in cfb expression were detected, with participants from the Srayov district exhibiting lower baseline and endline expression, than those from Prey Kuy and Tboung Krapeu.

Conclusions: Oral iron supplementation for 12 wk did not increase cfb expression in this population of predominantly iron-replete Cambodian women, compared with placebo. However, the observed geographic variation in cfb expression across districts suggests that environmental or behavioral factors may contribute to GBS colonization risk. These findings highlight the need to further investigate region-specific risk factors and provide a foundation for future research into GBS screening in Cambodia. This trial was registered at clinicaltrials.gov as NCT04017598.

Keywords: Cambodia; Group B Streptococcus; bacteria; dietary supplement; gene; gene expression; infection; intake; iron; microbe.